Implantable drug-delivery devices typically utilize an actuation mechanism to drive medicament from a reservoir through a cannula into target areas. The actuation mechanism may be pressure-driven or cause pressure changes within the drug-delivery device or at the interface between the device and its surroundings. The pressure magnitudes and gradients in these regions can make it difficult to precisely control delivery of small amounts of drug, especially when the device is refillable or used for repeated dosing over a relatively long period. For example, without proper regulation of the pressure in the drug reservoir, pressure or vacuum buildup can interfere with smooth, continuous administration of a liquid medicament. This problem is particularly acute in devices whose driving mechanism involves generation of pressurized gas. In such devices, excess gas can leak to various device regions. More generally, when the device is implanted in a patient, the difficulties of limited physical space and access to the device, as well as the overall complexity of in vivo implantation and operation, can make pressure regulation in the device essential and exacerbate the problems arising from inadequate regulation.
Gas-driven drug-delivery devices may produce excess gas, and ensuring gas-tightness along the pressurization route can require significant efforts in design, manufacture and quality control. For example, in electrolytic drug-delivery devices, hydrogen and oxygen are generated as an actuating mechanism during dosing. Hydrogen is known to penetrate thin walls easily and leak into reservoir chambers and their perimeters, resulting in inaccurate pressure-dosing characteristics or even unintended delivery of gas. For some drug-delivery regimes, instantaneous bursts of drug may be required (alone or to supplement steady-state delivery). The excess gas and its effects on delivery accuracy can be pose major challenges, especially in the sub-milliliter scale.
Excess gas can also adversely affect the refilling of drug-delivery devices. As excess gas accumulates in the drug reservoir chambers, refill routes, and/or other adjacent interior spaces, it can complicate the refilling process and create considerable dead volume. More importantly, some drug-delivery devices have compliant reservoir walls to minimize dead volumes and provide ease in handling during refilling. With these devices, the excess gas accumulating in the perimeter creates a differential pressure that can eventually prevent the refilling operation from proceeding to completion.
Venting may seem like an obvious solution to unwanted gas buildup, but can be difficult to achieve in devices intended for implantation. While valved passages connecting the pump to a region outside of the device body have been proposed for managing excess gas in drug-delivery devices, such an approach is often unsuitable for biomedical implants, as the transport of gases through the human body via a catheter or artificial vehicle for venting may be painful and increase risk of infection. In addition, as most biomedical implants are highly integrated and miniaturized, the limited physical space and access to the device further complicates venting: the venting component in an implantable drug-delivery device must generally be compact, easy to integrate and, notably, compatible with the anatomic environment in which various body fluids and tissues may interact with the vent.
One possible approach to venting an implantable drug-delivery device is to connect additional gas-filled space to the region of excess gas accumulation in order to buffer abrupt pressure changes inside the device. This may be additional space within the device itself or a chamber that is tethered by a fluidic connection but external to the main drug-delivery device. This approach, however, requires a relatively large space that may be impractical for biomedical applications that demand space efficiency. Additionally, without a passage through which excess gas may be expelled from the device, pressure will continue to build up within, and potentially overwhelm, the buffer volume. Another possible approach would employ a gas-permeable outer shell to expel excess gas. This approach, however, would pose challenges of material choice, fabrication complexity, fabrication cost, and compromised mechanical strength of the surface. Furthermore, pores that confer gas permeability can also allow for tissue ingrowth that may block a sufficient number of the pores to compromise their effectiveness.